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Neonatal Exposure to 6-n-Propyl-Thiouracil, an Anti-Thyroid Drug, Alters Expression of Hepatic DNA Methyltransferases, Methyl CpG-Binding Proteins, Gadd45a, p53, and PCNA in Adult Male Rats.

ABSTRACT: Background:Neonatal 6-n-propyl-2-thiouracil (PTU) exposure to male rats is reported to impair liver function in adulthood. However, the mechanism by which the drug impairs liver function is not well known. Objectives:The objectives of the study were to investigate the effects of neonatal exposure of PTU on the expression of DNA methyltransferases (DNMTs), methyl-DNA binding proteins (MBDs), Gadd45a, p53, and proliferating cell nuclear antigen (PCNA) in adult rat liver. Methods:The effects of neonatal transient (from birth to 30 days of age) and persistent (from birth to 90 days of age) treatment of PTU on DNA damage and on the expression of p53, PCNA, DNMTs, and MBDs were investigated at transcriptional and translational levels in male adult liver. Results:Persistent exposure to PTU from birth caused significant downregulation of expression of DNMT1 and DNMT3a and upregulation of DNMT3b, MBD4, and Gadd45a without any damage to DNA. Although MeCp2 transcripts were significantly low in the liver of adult rats after persistent exposure to PTU compared to controls, its translated products were significantly higher than in controls. The expression of p53 and PCNA in PTU-treated rats was significantly higher and lower, respectively, than that in control rats. Conclusion:The results suggest that neonatal exposure of male rats to PTU resulted in alteration in the expression of proteins that are associated with DNA methylation and genome stabilization in adult rat liver.

SUBMITTER: Bunker SK

PROVIDER: S-EPMC5704726 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Neonatal Exposure to 6-n-Propyl-Thiouracil, an Anti-Thyroid Drug, Alters Expression of Hepatic DNA Methyltransferases, Methyl CpG-Binding Proteins, Gadd45a, p53, and PCNA in Adult Male Rats.

Bunker Suresh Kumar SK Dandapat Jagneshwar J Chainy Gagan B N GBN Sahoo Sunil Kumar SK Nayak Prabhat Kumar PK

European thyroid journal 20170919 6

<h4>Background</h4>Neonatal 6-n-propyl-2-thiouracil (PTU) exposure to male rats is reported to impair liver function in adulthood. However, the mechanism by which the drug impairs liver function is not well known.<h4>Objectives</h4>The objectives of the study were to investigate the effects of neonatal exposure of PTU on the expression of DNA methyltransferases (DNMTs), methyl-DNA binding proteins (MBDs), Gadd45a, p53, and proliferating cell nuclear antigen (PCNA) in adult rat liver.<h4>Methods< ...[more]

PMID: 29234621

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Project description:BackgroundInfants born extremely premature are at increased risk for health complications later in life for which neonatal inflammation may be a contributing biological driver. Placental CpG methylation provides mechanistic information regarding the relationship between prenatal epigenetic programming, prematurity, neonatal inflammation, and later-in-life health.MethodsWe contrasted CpG methylation in the placenta and neonatal blood spots in relation to neonatal inflammation in the Extremely Low Gestational Age Newborn (ELGAN) cohort. Neonatal inflammation status was based on the expression of six inflammation-related proteins, assessed as (1) day-one inflammation (DOI) or (2) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 postnatal weeks). Epigenome-wide CpG methylation was assessed in 354 placental samples and 318 neonatal blood samples.ResultsPlacental CpG methylation displayed the strongest association with ISSI (48 CpG sites) but was not associated with DOI. This was in contrast to CpG methylation in blood spots, which was associated with DOI (111 CpG sites) and not with ISSI (one CpG site).ConclusionsPlacental CpG methylation was strongly associated with ISSI, a measure of inflammation previously linked to later-in-life cognitive impairment, while day-one neonatal blood methylation was associated with DOI.ImpactNeonatal inflammation increases the risk of adverse later-life outcomes, especially in infants born extremely preterm. CpG methylation in the placenta and neonatal blood spots were evaluated in relation to neonatal inflammation assessed via circulating proteins as either (i) day-one inflammation (DOI) or (ii) intermittent or sustained systemic inflammation (ISSI, inflammation on ≥2 days in the first 2 weeks). Tissue specificity was observed in epigenetic-inflammatory relationships: placental CpG methylation was associated with ISSI, neonatal blood CpG methylation was associated with DOI. Supporting the placental origins of disease framework, placental epigenetic patterns are associated with a propensity for ISSI in neonates.

Dataset Information

Neonatal Exposure to 6-n-Propyl-Thiouracil, an Anti-Thyroid Drug, Alters Expression of Hepatic DNA Methyltransferases, Methyl CpG-Binding Proteins, Gadd45a, p53, and PCNA in Adult Male Rats.

Publications

Neonatal Exposure to 6-n-Propyl-Thiouracil, an Anti-Thyroid Drug, Alters Expression of Hepatic DNA Methyltransferases, Methyl CpG-Binding Proteins, Gadd45a, p53, and PCNA in Adult Male Rats.

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